This program aims at gaining a better understanding of the etiology and pathogenesis of chronic degenerative and demyelinating diseases of man with emphasis on multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). In following this goal we are particularly interested in: (1) the molecular and cellular mechanisms by which viruses persist, escape immunologic surveillance and cause cell dysfunction; (2) humoral and cellular immune responses which serve to neutralize infectious agents and eliminate infected cells; (3) the environmental and genetic factors which predispose individuals to aberrant viral infections and aberrant immune responses; (4) the molecular and cellular events which mediate viral and/or immunologic destruction of cells and tissues leading to demyelination and degenerative diseases; and (5) applying data generated from these areas in basic research to the clinical investigation of patients with multiple sclerosis and amytrophic lateral sclerosis, and using leads obtained from the clinical investigation of patients with these and other neurologic disorders for basic research studies. In the proposed venture, we intend to combine the skills of investigators with expertise in experimental biology, immunology, virology, molecular biology, neuropathology, biochemistry and cell biology. With this team we shall continue our efforts in mounting a concentrated exertion towards understanding the cause, pathogenesis and hopefully therapeutic approach to correcting the degenerative and demyelinative disorders of the nervous system.